Bioterrorism: A Public Health Issue

Biological warfare has existed for centuries. Examples include the Mongols catapulting plague-infested bodies into Caffa to break a siege in 1346 and in 1763, blankets used by smallpox victims being given to American Indians at Fort Pitt. During World War II and the “Cold War” era, many nations, including the United States, had active biological weapons research programs, and there is evidence of some limited biological weapons use during that war. A 1972 international agreement to ban biological weapons was ratified by 140 nations, but included no verification mechanism. Evidence supports violation of this treaty. In 1979 an accidental release of anthrax in Sverdlovsk, Russia, occurred from a secret bioweapons plant. At least 66 people working or living downwind from the facility died of pulmonary anthrax. In 1992, Russian president Boris Yeltsin admitted that the Soviets had an active biological weapons program until that year. Currently at least 17 nations are believed to have offensive biological weapons programs(1).

Bioterrorism – the use of biological agents to intentionally produce disease in susceptible populations to meet terrorist aims-has become an increasing concern throughout the world, including the United States. Information on how to construct chemical or biological weapons is available on the Internet. While still requiring a high level of expertise and financial resources, advances in biotechnology have made the production and dissemination of pathogenic organisms or chemical toxins a real possibility. For example, Aum Shinrikyo, a Japanese cult, is known for having released sarin gas in a Tokyo subway in 1995. Over 5,500 people sought medical treatment; 20 percent were hospitalized and 12 people died. The cult was found to have facilities producing both chemical and biological weapons, and had attempted the release of botulinum toxin and anthrax spores without success.

No one can say for sure how likely it is that a bioterrorist attack will occur in the United States in the next several years, though some believe it is a significant threat, particularly related to concerns regarding doomsday cult reactions to the millenium. There is agreement, however, that it is essential for the government, public health community, and medical profession to be prepared for this type of health emergency, just as it is necessary to be prepared for natural disasters. It is tempting to believe that Vermont is not at any risk for being the target of such an attack.

However, it is not possible to be sure that an event will not happen here. An attack could be focused at a site considered less well prepared to respond. In addition, Vermont could be affected by an event occurring in New York City, Boston, or even distant parts ofthecountry.Bioterrorismpreparednessalsoincludestheability to respond appropriately to threats such as anthrax hoaxes. Nationally, anthrax threats increased dramatically after publicity of the arrest in February, 1998 of a white supremacist who had threatened to release anthrax in Las Vegas(2). Vermont was among states experiencing anthrax hoaxes this year.

Early detection of a bioterrorist attack is crucial. Some agents cause diseases that could have relatively short incubation periods, and have high mortality rates when proper treatment is not initiated early in the course of infection. Morbidity and mortality can be greatly reduced by early identification, prophylaxis of those exposed, and appropriate early treatment of the infected. For agents that can be transmitted from person-to-person, it is obviously even more crucial to identify the disease early. To detect unusual illnesses caused by intentionally released agents, a high index of suspicion must be maintained, and suspicious illnesses should be reported before they are confirmed. This may enablethe Health Department to detect trends in what appears at first to be sporadic disease.

The initial detection of an unannounced bioterrorist attack would rely on both the diagnostic capabilities of physicians and other health care providers, and the ability of public health surveillance to detect unusual patterns of disease. The following situations could suggest a bioterrorism event, and should be reported to the Health Department:

Single, definitively diagnosed or strongly suspected case ofillnessduetoapotentialbioterroristagentoccurringinapatient with no known risk factor.

Cluster of patients presenting with a similar syndrome that includes unusual disease characteristics or unusually high morbidity or mortality without an obvious etiology.

Unexplained increase in a common syndrome above seasonally expected levels.

The CDC has listed several potential agents of particular concern, including Bacillus anthracis (anthrax), smallpox virus, Yersinia pestis (plague), Clostridium botulinum toxin, and Francisella tularensis (tularemia). Identification of these agents would be difficult because they are not expected, many have non-specific presenting symptoms, and health care providers are not familiarwiththem.Theclinicalfeaturesofanthraxandsmallpox, two agents most frequently mentioned as possible bioterrorism agents, are described below. The information below is from the U.S. Army Medical Research Institute of Infectious Diseases (3), and two recently published consensus statements (4, 5).

Anthrax:Bacillus anthracis is a rod-shaped, gram-positive sporulating organism; the spores are the usual infective form. While primarily a zoonotic disease, human illness can occur in people working with animals or animal products. While anthrax can occur in cutaneous or gastrointestinal forms, inhalational anthrax is the chief bioterrorism concern.

After an incubation period averaging one to six days, inhalational anthrax presents as fever, malaise, fatigue, cough, mild chest discomfort and possibly vomiting or abdominal pain. This stage lasts for hours or days. In untreated patients, there may or maynotbeabriefperiodofimprovement;thepatientthenabruptly develops severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Shock and death occur within 24-36 hours after onset of severe symptoms. Physical findings are initially nonspecific; as disease progresses, the chest x-ray may reveal a widened mediastinum with or without pleural effusions. Bacillus anthracis can be detected by Gram stain of blood and by blood culture, but often not until late in the course of illness.

Treatment with antibiotics early in the course of symptoms is crucial; once patients have developed significant symptoms, the mortality rate is high. Most naturally occurring strains of anthrax are sensitive to penicillin, however, the possibility of a penicillin-resistant strain must be considered. A recently published consensus statement “Anthrax as a Biological Weapon: Medical and Public Health Management” (4), recommends ciprofloxacin for treatment or prophylaxis of exposed adults and children until susceptibility to penicillin is confirmed. Anthrax is not transmitted person-to-person. Prophylaxis for those exposed to aerosolized anthrax would require a 60 day antibiotic regimen, though shorter duration may be recommended if anthrax vaccine is used in conjunction with antibiotic. For individuals involved in an incident with threatened exposure to anthrax, personal decontamination is rarely if ever needed unless the individual has had direct contact with the substance alleged to be anthrax.

Smallpox: Smallpox was declared eradicated by the World Health Organization in 1980. Two repositories were approved to hold the remaining variola virus. These two reference laboratories are the Centers for Disease Control and Prevention (CDC) in Atlanta and a laboratory in Moscow. However, during the past several years allegations have been made that smallpox virus was weaponized in the Soviet Union, and there is concern that virus stores may have been moved to additional sites. Routine vaccination for smallpox in the United States was discontinued among civilians in 1972. The immune status of individuals vaccinated before that time is not certain, but immunity is believed to decline substantially within 10 years of vaccination. Thus, worldwide there is high susceptibility to this infection (5).

Smallpox is caused by variola virus, which is an Orthopox virus. Transmission is person to person by respiratory discharges (droplet nuclei or aerosols), by direct contact with skin lesions, or contact with contaminated bedding or clothing. The incubation period averages 12 to 14 days (range 7-17 days). Individuals are not infectious until onset of rash.

Smallpox infection begins with abrupt onset of fever, malaise, rigors, vomiting, headache and backache. During this stage of illness about 10 percent of lighter-skinned patients have an erythematous rash. Lesions appear two to three days later. As opposed to chickenpox, smallpox lesions are more numerous on the face and extremities, occur on the palm, and develop synchronously. Mortality is approximately 30 percent; death is thought to occur from toxemia associated with circulating immune complexes and soluble variolaantigens(5). Two other clinical presentations, hemorrhagic-type smallpox and flat-type or malignant smallpox, occur in approximately 10 percent of cases and have a high mortality rate. Laboratory confirmation of infection would be essential and would need to be performed at the CDC’s biosafety level 4 laboratory.

There is currently no chemotheraputic agent known to be effective in the treatment of smallpox; only supportive care could be provided. Potential antiviral agents are undergoing investigation. Prophylaxis for individuals known to be exposed would be vaccination, which should provide some level of protection if given within four days of exposure. The supply of stockpiled vaccine in the United States is limited and estimated to be sufficient for vaccinating six to seven million people (5). Serious complications can occur in vaccinated individuals, requiring the use of vacciniaimmuneglobulin(VIG). Availability of VIG is also extremely limited. Both smallpox vaccine and VIG would only be made available by the CDC through state health departments.

Conclusion

The intentional release of a biologic agent would be a public health emergency. Early detection would be essential to minimizing the impact of such an event. Clinical suspicion and prompt reporting by physicians and other health care providers of any unusual disease clusters or manifestations to the Health Department is key to the early recognition of both natural outbreaks and bioterrorist events.

References:

US Army Medical Research Institute of Infectious Diseases. Medical Management of Biological Casualties. 3rd ed. Fort Detrick, Frederick Md. US Army Medical Research Institute of Infectious Diseases. 1998.

Escherichia coli O157:H7 in Vermont: 1994-1999

E. coli O157:H7 is one of hundreds of strains of the bacterium Escherichia coli. Most of the strains do not cause illness and live in the intestines of healthy people and animals. However, the strain designated as O157:H7 produces a toxin that can cause serious illness. The combination of letters and numbers in the name refer to specific markers that distinguish it from other E. coli. E. coli O157:H7 was first recognized as a human pathogenin 1982 during an outbreak traced to contaminated hamburgers. It is an emerging cause of food borne illness throughout the United States and Vermont.

E. coli O157:H7 infection can produce a number of symptoms, often including bloody diarrhea and occasionally a serious kidney complication called hemolytic uremic syndrome (HUS). The diarrhea experienced may range from none or very mild and non-bloody to severe bloody dysentery with abdominal cramps. Usually little or no fever is present. Humans of any age can become infected, but children under five years of age and the elderly are more likely to develop serious complications. About 2 percent to 7 percent of infections lead to the potentially life-threatening condition HUS. In HUS blood cells are destroyed and kidneys may fail; blood transfusions and kidney dialysis are often required. In the United States, it is estimated that with intensive care the death rate for HUS is 3 percent to 5 percent. Most people with HUS recover completely, but about one third have abnormal kidney function many years later, and a few require long-term dialysis.

The symptoms of E. coli O157:H7 infection usually occur about three days (range one to nine days) after consuming a contaminated, undercooked product. Most infected people recover without specific treatment in 5 to 7 days. The efficacy of antibiotics has not been proven and anti-diarrheal medication should be avoided.

The infection is usually acquired by eating food containing the bacterium. Contamination of meat can occur during slaughter and organisms can be mixed with the beef when it is ground. Eating beef which is rare or improperly cooked is the most common way of contracting the infection. Drinking unpasteurized milk and swimming in, or drinking, sewage-contaminated water may also cause infection. Other food products such as lettuce, sprouts and unpasteurized juices have been associated with infections. Person-to-person transmission can also occur if infected individuals do not adequately wash hands after using the toilet or changing the diapers of an infected child. Young children may shed the organism in their feces for a week or two after the illness resolves. Family members and playmates of infected toddlers are at risk of becoming infected. Infected children should be excluded from swimming or attending day care until two negative stool specimens taken 48 hours apart have been obtained.

The best way to prevent E. coli O157:H7 infection is to avoid rare or undercooked (pink) hamburger and other ground beef products. Make sure that cooked meat is brown throughout (no pink) and that the juices run clear. Contaminated meat may look and smell normal.

E. coliO157:H7 became reportable in Vermont on October 4, 1994. From 1994 to August 1, 1999 a total of 122 confirmed and epidemiologic-linked cases have been reported (Figure 1) with annual rates per 100,000 persons (based on 1996 total Vermont populationestimates)rangingfrom1.4in1997to6.3in1996.Fifty percent of the cases were in females and 50 percent in males. The median age for the 1994-1999 period was 17 years with a range of 2 months to 87 years (Figure 2). Hospitalization was reported for 40 cases (33 percent) during the 1994-1999 time period and one death occurred in a 57 year old. Four cases of HUS were reported during the period with ages of 5, 12, 57 and 66.

Providers are encouraged to test for E. coli O157:H7 in patients with bloody diarrhea. Not all enteric screens test for E. coli O157:H7 unless specifically requested. For further information on E. coli O157:H7, contact the Vermont Department of Health Infectious Disease Epidemiology at 863-7240 or 1-800-640-4374.

Chronic Disease in Vermont: Osteoporosis

Osteoporosis is a silent disease—the first sign is often a fracture. One in three women and one in eight men age 50 and older will break a bone during their lifetime due to osteoporosis (1). While Caucasian and Asian women are at highest risk, women of all racial and ethnic groups and men are also at significant risk. Nationwide, health care costs for osteoporotic fractures are estimated at $13.8 billion per year (2).

Prevalence

Osteoporosis is now defined on the basis of bone mineral density (BMD). Prevalence data are in exact:There are few data on men, Hispanics or American Indians. Most prevalence estimates are based on Caucasian females. Nationally, an estimated 13 to 18 percent of women and 1 to 4 percent of men age 50 and older have osteoporosis; an additional 37 to 50 percent of women and 28 to 47 percent of men age 50 and older have low bone mass (3). Based on extrapolations from national estimates, 21 percent of Vermont women and 6 percent of Vermont men age 50 and over—almost 21,500 older Vermonters—have osteoporosis (4). These figures are slightly higher than the national averages and are expected to increase as the population ages.

Impact

From 1993 to 1997,there were 2,594 Vermont resident hospitalizations (2,333 females and 261 males) due to osteoporosis-related conditions, with an average annual cost of nearly $4.7 million. For Vermonters age 50 and older, the annual hospitalization rate from 1993 to 1997 was 5.6 per 1,000 women and 0.7 per 1,000 men, and the average length of stay was five to nine days(5).

The most common osteoporotic fractures are of the vertebrae and the hip. Hip fractures are the most serious and costly: One-half of patients become permanently disabled and 20 to 25 percent require long-term care (1). The mortality rate within the first year following a hip fracture is 15 to 20 percent higher than expected for a given age group(6). Ninety percent of hip fractures in women and 80 percent in men are attributable to osteoporosis (7).

Risk factors and interventions

Nonmodifiable risk factors include age, family history, Cau-casian or Asian race, and female gender. Women are at higher risk due to achieving a lower peak bone mass and having accelerated bone loss rates in the five to seven years following menopause. Modifiable risk factors include estrogen deficiency, low lifelong calcium intake, smoking, low body mass, inadequate physical activity, alcoholism, certain conditions such as hyperparathy-roidism, and certain medications including anticonvulsants and glucocorticoids (8). Other factors such as poor balance or vision can increase the risk for falls.

Routine screening is not recommended, as there are no data on cost or effectiveness of testing and treatment. Instead, BMD testing is recommended for those at greatest risk and to help in making decisions about treatment options. The National Osteoporosis Foundation (NOF) recommends testing for all post-menopausal women under age 65 who have one or more risk factors, all women age 65 and older regardless of risk factors, all women past menopause who have had a fracture,andwomenwho have been on hormone replacement therapy for prolonged periods. While there are no federal or state mandates that insurers cover BMD testing, Medicare now covers these tests for beneficiaries who are estrogen-deficient, on long-term steroid therapy, currently taking drugs for osteoporosis, have spinal abnormalities suggesting low bone mass, or have an overactive parathyroid gland. Several types of BMD tests are available. These tests have varying levels of accuracy and precision, but all are good predictors of fracture risk (8). Several drugs have been approved by the FDA for the prevention and treatment of osteoporosis. In general, these drugs appear to reduce some fractures by 25 to 50 percent (8).

Prevention

While older adults suffer the consequences of osteoporosis, this disease begins early in life. A healthy lifestyle in childhood and adolescence can set the stage for optimum bone mass. Variations in calcium intake early in life may account for a five to 10 percent difference in adult bone mass and a 50 percent difference in the hip fracture rate later in life(9). Adolescents with eating disorders may be at particular risk due to both poor nutrition and amenorrhea. An active lifestyle not only increases bone density but improves strength and balance, reducing the risk of falls (8).

Prevention messages across the lifespan should include:

Get adequate amounts of calcium—at least 1200 mg/day.

Get adequate amounts of Vitamin D—at least 400 IU/day.

Live an active lifestyle.

Avoid tobacco.

Drink alcohol in moderation if at all.

Additional preventive measures for older adults should include:

Consider BMD testing if at high risk.

Based on BMD results, consider drug treatment.

Fall-proof your home.

A physician’s guide to testing, treatment, and prevention is available through the NOF at (202) 223-2226 or URL <http:// www.nof.org>. For Vermont information, contact Kathy Backes at the New England Dairy and Food Council at(802) 863-5416, or Jill Nye-McKeown, Chair of Vermont’s interagency Osteoporosis Task Force at (802) 862-9622.

Selected Reportable Diseases Vermont, Year to Date (08/28/99)

October is Celiac Awareness Month

Celiac disease (also referred to as celiac sprue, nontropical sprue, or gluten sensitive enteropathy) is a genetic digestive disorder triggered by the consumption of gluten, the common name for a type of protein found in all forms of wheat, rye, barley and possibly oats. It can be difficult to diagnose given the wide range of symptoms. While some people experience extreme gastrointestinal discomfort, others experience neurological symptoms, such as tingling in the fingers and toes, or headaches.

If you have patients with celiac disease, please let them know about the Celiac Support Group of Vermont, PO Box 878, Shelburne, VT 05482, telephone 985-4020 or 860-7105.

Vaccine Advisory: Thimerosal, Rotavirus Vaccine
July 1999

Thimerosal, a mercury-based preservative, has been used as an additive to prevent and/or kill bacteria in some vaccines since the 1930’s. The Food and Drug Administration recently conducted a review that recognized that some children could be exposed to a cumulative level of mercury over the first six months of life that exceeds a measure for mercury established by the Environmental Protection Agency. To date, there has been no data or evidence of any harm caused by the level of exposure that some children may have encountered with the existing immunization schedule. The larger risk of not vaccinating children far outweighs the unknown and probably much smaller risk, if any, of cumulative exposure to thimerosal-containing vaccines over the first six months of life (MMWR7/9/99/Vol.48/No.26).

The United States Public Health Service and the American Academy of Pediatrics have advised practitioners to delay giving hepatitis B vaccine to newborns of hepatitis B surface antigen (HBsAg) negative mothers due to the presence of thimerosal. All other vaccines currently provided by the Vermont Department of Health (VDH) and administered in the first six months of life are thimerosal free. The VDH recommends the following:

1.Documentation of the mother’s HBsAg status at delivery

Rigorous protocols should be in place to document the HBsAg status of every pregnant woman to reduce the possibility of perinatal transmission. Test results should be available for review at the time of delivery.

2.Vaccination at birth of infants born to HBsAg positive mothers or mothers of unknown status

No change in the current recommendations that hepatitis B vaccine and hepatitis B immune globulin be administered within 12 hours of birth to infants of HBsAg positive women, and hepatitis B vaccine for those infants born to women whose status is unknown.

3.Routine vaccination of infants born to HBsAg negative mothers

Dose 1 of hepatitis B vaccine should be routinely administered in the range of 2 – 6 months of age, with the series completed by 18 months. When a thimerosal free hepatitis B vaccine is available, we anticipate a return to routine universal hepatitis B vaccination of newborns.

Postpone Administration of Rotavirus Vaccine

The Centers for Disease Control and Prevention (CDC) recommends that healthcare providers discontinue the use of rotavirus vaccine for infants, at least until November, 1999 based on early surveillance reports of intussusception among some infants who received rotavirus vaccine. Although intussusceptions occur among infants who have not received rotavirus vaccine,CDC will be collecting additional data in the next several months that may indicate more clearly whether the rotavirus vaccine increases the risk of intussusception. The recommendation is being made with the consideration that rotavirus season is still 4 – 6 months away in most parts of the United States.